Ozonolysis of the double bond of the unsaturated uronate residue in low molecular weight heparin and K5 heparosan

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Authors
Masuko, Sayaka
Higashi, Kyohei
Wang, Zhenyu
Bhaskar, Ujjwal
Hickey, Anne Marie
Zhang, Fuming
Toida, Toshihiko
Dordick, Jonathan S.
Linhardt, Robert J.
Issue Date
2011-01-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Ozone is known to add across and cleave carbon-carbon double bonds. Ozonolysis is widely used for the preparation of pharmaceuticals, for bleaching substances and for killing microorganisms in air and water sources. Some polysaccharides and oligosaccharides, such as those prepared using chemical or enzymatic β-elimination, contain a site of unsaturation. We examined ozonolysis of low-molecular-weight heparins (LMWHs), enoxaparin and logiparin, and heparosan oligo- and polysaccharides for the removal of the nonreducing terminal unsaturated uronate residue. 1D (1)H NMR showed that these ozone-treated polysaccharides retained the same structure as the starting polysaccharide, except that the C4-C5 double bond in the nonreducing end unsaturated uronate had been removed. The anticoagulant activity of the resulting product from enoxaparin and logiparin was comparable to that of the starting material. These results demonstrate that ozonolysis is an important tool for the removal of unsaturated uronate residues from LMWHs and heparosan without modification of the core polysaccharide structure or diminution of anticoagulant activity. This reaction also has potential applications in the chemoenzymatic synthesis of bioengineered heparin from Escherichia coli-derived K5 heparosan.
Description
Carbohydrate Research, 346, 1962–1966
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Full Citation
Ozonolysis of the double bond of the unsaturated uronate residue in low molecular weight heparin and K5 heparosan, S. Masuko, K. Higashi, Z. Wang, U. Bhaskar, A. M. Hickey, F. Zhang, T. Toida, J. S. Dordick, R. J. Linhardt, Carbohydrate Research, 346, 1962–1966, 2011.
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Elsevier
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1873426X
86215
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